A 6 Month Randomized, Double-blind, Placebo-controlled Study Followed by a 6 Month Open- Label Extension to Assess the Efficacy and Safety of Inclisiran as Monotherapy in Chinese Adults With Low or Moderate ASCVD Risk and Elevated Low-density Lipoprotein Cholesterol
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 207
- 试验地点
- 28
- 主要终点
- Percentage Change in Low-density Lipoprotein Cholesterol (LDL-C) (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part
研究概览
简要总结
The purpose of this study was to evaluate the efficacy and safety of inclisiran as a monotherapy in Chinese adults with low or moderate atherosclerotic cardiovascular disease (ASCVD) risk and elevated low-density lipoprotein cholesterol (LDL-C) who were not on any lipid lowering therapy.
详细描述
This study was designed as a randomized, double-blind, multi-center Phase III trial, with a placebo-controlled treatment period and an open label treatment period, to evaluate the efficacy and safety of inclisiran sodium 300 mg s.c. in participants aged 18 to 75 years with a low or moderate ASCVD risk and fasting LDL-C value of ≥ 130 mg/dL but < 190 mg/dL who were not on any lipid lowering therapy.
The study consisted of 3 parts:
- Screening: the screening period was up to 14 days to allow adequate time for the eligibility evaluations.
- Core Part: a double-blind, placebo-controlled treatment period of 180 days in which eligible participants were randomized 1:1 to receive either inclisiran sodium 300 mg s.c.
(inclisiran group) or matching placebo s.c. (control group) on Day 1 and Day 90. The end of core part (EOC) visit was conducted on Day 180. The database lock for the core part was planned to occur after all randomized participants have completed the EOC visit (or have discontinued from the study before EOC). The primary analysis was conducted after the database lock for the core part.
• Extension Part: an extended treatment period of 180 days. In the extension part, participants originally randomized to inclisiran in the core part were to continue the inclisiran treatment while participants initially randomized to placebo were to transit to the inclisiran. The extension part was to start from the Day 180 treatment dose (placebo in the inclisiran group and inclisiran for participants originally randomized to the control group).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Sponsor Personnel participating in the study conduct were also blinded during the during core part of the study.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent must be obtained before any assessment is performed.
- •Fasting LDL-C of ≥ 130 mg/dL but < 190 mg/dL
- •Triglycerides ≤ 400 mg/dL
- •Categorized as low or moderate ASCVD risk by the 2016 Chinese Guideline
排除标准
- •Use of any LLT within 90 days prior to screening visit
- •History of ASCVD
- •Diabetes mellitus or fasting plasma glucose of ≥ 7.0 mmol/L or HbA1c ≥ 6.5%
- •Secondary hypercholesterolemia, e.g. hypothyroidism or nephrotic syndrome
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
Inclisiran - Inclisiran
Inclisiran sodium 300 mg (equivalent to 284 mg inclisiran) s.c administered on Day 1, Day 90, and Day 270, and placebo on Day 180
干预措施: Inclisiran (Drug)
Inclisiran - Inclisiran
Inclisiran sodium 300 mg (equivalent to 284 mg inclisiran) s.c administered on Day 1, Day 90, and Day 270, and placebo on Day 180
干预措施: Matching Placebo for Inclisiran (Drug)
Placebo- Inclisiran
Placebo on Day 1 and Day 90 and Inclisiran sodium 300 mg (equivalent to 284 mg inclisiran) s.c on Day 180 and 270
干预措施: Inclisiran (Drug)
Placebo- Inclisiran
Placebo on Day 1 and Day 90 and Inclisiran sodium 300 mg (equivalent to 284 mg inclisiran) s.c on Day 180 and 270
干预措施: Matching Placebo for Inclisiran (Drug)
结局指标
主要结局
Percentage Change in Low-density Lipoprotein Cholesterol (LDL-C) (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part
时间窗: Baseline, Day 150
Low-density lipoprotein cholesterol is a type of lipoprotein in the blood. Lipoproteins are particles made of lipids(fats) and proteins that carry fats through the bloodstream. Because of their structure, fats can't move through the blood on their own. So, lipoproteins carry fats to various cells in the body.
次要结局
- Absolute Change in Log-transformed Lp(a) (Nmol/L) From Baseline at Day 150 - Core Analysis: Core Part(Baseline, Day 150)
- Percentage Change in Triglyceride (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part(Baseline, Day 150)
- Absolute Change in Triglyceride (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part(Baseline, Day 150)
- Number of Participants With Adverse Events (AEs) During Core Part(Core part, from treatment start (Day 1) to Day 150)
- Number of Participants With Adverse Events (AEs) During Extension Part(Extension part, from Day 181, up to Day 360)
- Percentage Change in LDL-C (mg/dL) From Baseline at Day 330 - Final Analysis: Core Part + Extension Part(Baseline, Day 330)
- Absolute Change in LDL-C (mg/dL) From Baseline at Day 330 - Final Analysis: Core Part + Extension Part(Baseline, Day 330)
- Number of Participants With Adverse Events (AEs) - Cumulative Data (Core + Extension Part)(AEs are reported from first dose of study treatment until end of study treatment plus 30 days after the last study visit (or 90 days after the last administration of study drug, whichever is longer) up to a maximum timeframe of approximately 360 days)
- Absolute Change in LDL-C (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part(Baseline, Day 150)
- Percentage Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) (ng/mL) From Baseline at Day 150 - Core Analysis: Core Part(Baseline, Day 150)
- Absolute Change in PCSK9 (ng/mL) From Baseline at Day 150 - Core Analysis: Core Part(Baseline, Day 150)
- Absolute Change in HDL-C (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part(Baseline, Day 150)
- Percentage Change in Total Cholesterol (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part(Baseline, Day 150)
- Absolute Change in Total Cholesterol (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part(Baseline, Day 150)
- Percentage Change in Non-HDL-C (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part(Baseline, Day 150)
- Absolute Change in Non-HDL-C (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part(Baseline, Day 150)
- Percentage Change in Apolipoprotein B (ApoB) (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part(Baseline, Day 150)
- Absolute Change in ApoB (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part(Baseline, Day 150)
- Percentage Change in Apolipoprotein A-1 (ApoA-1) (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part(Baseline, Day 150)
- Absolute Change in ApoA-1 (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part(Baseline, Day 150)
- Percentage Change in Lipoprotein (a) (Lp(a)) (Nmol/L) From Baseline at Day 150 - Core Analysis: Core Part(Baseline, Day 150)
- Percentage Change in High-density Lipoprotein Cholesterol (HDL-C) (mg/dL) From Baseline at Day 150 - Core Analysis: Core Part(Baseline, Day 150)